Diabetic retinopathy (DR) is a leading cause of visual impairment in the working age population. Treatment for severe retinopathy and macular edema has relied on the presence of clinical signs visible through fundus photography or invasive fluorescein angiography. However, advances are being made in the early treatment that should prevent such proliferative changes or edema from occurring. Implementation of such preventive strategies will require the early detection of the onset of diabetic eye disease, such as changes in retinal blood flow, retinal thickness and volume, and decreases in retinal oxygenation. Current techniques are not able to provide detailed retinal structures, retinal map, or summary of the blood flow or oxygenation within the retina that might trigger such an intervention. In anticipation of the imaging needs required by the treatment advances, this research grant proposes to develop, test, and provide normative data on parameters of retinal tissue structures, blood flow, and oxygenation. Quantitative flow measurements will be made using laser speckle tracking approaches while oxygen saturation will be determined by spectral techniques within the visible and near-infrared range. Retinal oxygenation is established using laser illumination at a series of carefully chosen wavelengths. Each of these illumination wavelengths used for oxygenation also provides a separate flow estimate. Choice of the particular wavelength for flow assessment will provide a degree of discrimination between vasculature in the retina and in the fundus. These retinal maps of flow and oxygenation will be perfectly registered as the same camera is used for each assessment. In addition, the Stratus Optical Coherence Tomography system will be employed to evaluate retinal thickness and volume. The assessment of retinal thickness and volume, blood flow, and oxygenation, as well as standard fundus photography, will be performed in 100 diabetic patients identified from the Wilmer Retina Division: 50 with early signs of DR and 50 without signs of DR. In addition, 150 patients without diabetes will be recruited to provide normative data. Correlations of early changes in the absence of signs of DR, as well as in early signs of DR, will be evaluated. The proposed project will provide clinicians with invaluable tools, using relevant clinical measures of tissue structures, blood flow, and oxygenation, to guide early treatment of DR, with the ultimate goal of halting progression of early signs of the disease and preventing vision loss. Diabetic retinopathy is the leading cause of vision loss in working age adults. New treatment modalities to prevent the onset of eye disease and clinical trial outcomes that monitor these treatments are a high priority for the National Institutes of Health and the National Eye Institute. The proposed project seeks to create and test novel methods of assessing retinal oxygenation and blood flow, coupled with retinal thickness and volume, that can be used to determine the earliest signs of diabetic eye disease. Such methods will be critically important to assessment of preventive interventions and monitoring diabetic eye disease in the future.